Definitions and descriptions of key terms
| Precision oncology—An umbrella term underscoring the personalized management of cancer patients. Precision oncology includes both the diagnostic methods required to individualize treatment of each patient’s malignancy and the treatments administered based on the results of precision testing thereafter. The diagnostic methods may evaluate protein expression, cytogenetics, and mutations identified within tumor DNA. Examples of precision treatments include targeted therapies and immune checkpoint inhibitors. Non–small cell lung cancer (NSCLC)—A broad collection of histologic findings identified in patients with lung cancer. Approximately 85% of lung cancers include NSCLC histologic findings, while 15% are small cell lung cancers. The 2 most commonly diagnosed NSCLCs are adenocarcinoma and squamous cell carcinoma. The rate of actionable mutations is far greater in patients with adenocarcinoma than in those with squamous cell carcinoma. Driver mutation—A genetic alteration that provides a tumor cell with a fundamental growth advantage compared with normal tissue. If a targeted therapy has been discovered and validated among cancer patients harboring a specific driver mutation, the mutation may also be actionable. If a driver mutation has been studied extensively and is related to a better or worse prognosis, the mutation may be clinically relevant regardless of actionability. Passenger mutation—A mutation discovered within tumor DNA that does not drive tumorigenesis. Patients may have both driver and passenger mutations. Clinically relevant mutation—Mutations or alterations that may alter the course of treatment for a given patient with a specific cancer. Clinically relevant mutations may be predictive of response to targeted therapies or prognostic for standard treatment approaches. Actionable mutation or actionable alteration—Genetic mutations or alterations that correlate with response to targeted therapies. Mutations may be within oncogenes, thereby driving tumorigenesis, or tumor suppressor genes, thereby limiting mechanisms that mitigate tumorigenesis. Mutations most frequently correspond with increased or decreased activity of critical proteins. Targeted therapies commonly exert their effects on these specific proteins. On the other hand, cytotoxic chemotherapy often drives mutations in tumor DNA, which encourages cell apoptosis. Chromosomal rearrangement—A form of genetic alteration in which 2 chromosomes are fused in abnormal combinations. The resulting proteins may drive cellular neoplastic transformation. In patients with NSCLC, rearrangements involving the ALK and ROS1 genes are associated with response to targeted therapies. | Targeted treatment/therapy/agent—Drugs that specifically treat the proteins resulting from actionable genetic alterations. Within the realm of metastatic NSCLC, the most commonly prescribed targeted therapies are tyrosine kinase inhibitors (TKIs), which target the hyperactivity of the epidermal growth factor receptor. Precision testing—Diagnostic tests conducted on resected tumor samples or tumor DNA collected and centrifuged from the blood of cancer patients that evaluate the potential response to targeted therapies. Protein expression, chromosomal rearrangements, and tumor DNA sequencing may be evaluated by precision testing. Immunohistochemical (IHC) staining—A technique used by pathologists to visualize antigens (proteins) expressed on tumor cells. Two types of antibodies are used to indicate antigen: one antibody binds to the antigen, and another fluorescently labeled antibody binds to the antigen-antibody complex, thereby confirming the expression of a specific protein. Fluorescence in situ hybridization (FISH)—Similar to IHC, FISH analysis uses patient tissue samples for a histology-based assay of genetic variants. However, unlike IHC, FISH probes are predicated on complementary binding that can identify specific genetic sequences of interest. Using fluorescently labeled DNA or RNA probes created to reciprocally bind targets of interest, FISH analyses are able to detect the presence of their target sequences, and thus genetic variants, within prepared tissue samples. Tumor DNA sequencing—A broad term encompassing the various modalities to evaluate tumor DNA for mutations that may be clinically relevant. The DNA findings from a patient’s tumor sample are compared with standard databases to confirm the presence of mutations. Tumor DNA sequencing may assess the DNA of certain genes, whole exomes, or the entire genome. Next-generation sequencing (NGS)—A form of tumor DNA sequencing in which massive amplification of preselected portions of tumor DNA can be evaluated concurrently. Several complementary DNA probes are affixed to comprehensive NGS plates that allow for multiple portions of DNA to be sequenced simultaneously. The data output may be in the form of fluorescence, temperature, or current change, depending on the design of the NGS platform. Given the large volume of data generated concurrently, large-scale automated algorithms are required to process cumulative sequencing information. Liquid biopsy or plasma genotyping—A form of NGS that is conducted on DNA from dead tumor cells identified in the blood of patients with cancer. Liquid biopsy requires the collection and separation of circulating tumor DNA using advanced centrifuge techniques. |